霉酚酸酯对包括SARS-CoV-2在内的冠状病毒具有广谱抗病毒活性。

IF 4 3区 医学 Q2 VIROLOGY
Mengyuan Wu, Kun Wang, Huiqiang Wang, Haiyan Yan, Shuo Wu, Ge Yang, Yuhuan Li, Yongsheng Che, Jiandong Jiang
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引用次数: 0

摘要

背景:新的抗冠状病毒药物正在不断开发,以应对众多SARS-CoV-2变体带来的严重长期挑战。临床免疫抑制剂霉酚酸酯(MMF)和霉酚酸(MPA)已被报道具有抗冠状病毒活性。然而,尚未进行系统的研究来评估它们对包括SARS-CoV-2在内的泛冠状病毒的活性和机制。方法:采用qRT-PCR、Western blotting和免疫荧光法检测MMF和MPA的抗病毒作用。通过细胞热移法和Western blotting检测MMF对IMPDH的抑制作用。结果:MMF和MPA对包括HCoV-229E、HCoV-OC43、SARS-CoV-2祖先株及其变体在内的冠状病毒均有广谱抑制作用。就其特性而言,MMF在病毒感染的早期阶段起作用,通过与肌苷-5′-单磷酸脱氢酶(IMPDH)相互作用,阻断嘌呤核苷酸合成,从而抑制病毒复制。因此,MMF的抗病毒作用可被外源性鸟苷逆转。此外,MMF与molnupiravir、GC376或E64d联合使用显示出协同抗病毒作用。结论:MMF和MPA通过抑制IMPDH活性发挥广谱抗冠状病毒作用。MMF与其他药物联用时具有协同抗病毒作用,具有潜在的临床抗病毒应用价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mycophenolate mofetil exerts broad-spectrum antiviral activity against coronaviruses including SARS-CoV-2.

Background: New anti-coronavirus drugs are continuously being developed to address the serious long-term challenge posed by numerous SARS-CoV-2 variants. The clinical immunosuppressants mycophenolate mofetil (MMF) and mycophenolic acid (MPA) have been reported to have anti-coronavirus activities. However, systematic studies have not been conducted to evaluate their activities and mechanisms against pan-coronaviruses, including SARS-CoV-2.

Methods: The antiviral effect of MMF and MPA was determined by qRT-PCR assay, Western blotting, and immunofluorescence assay. The IMPDH inhibition effect of MMF was determined by cellular thermal shift assay and Western blotting.

Results: We showed that MMF and MPA had broad-spectrum inhibitory effect against coronavirus, including HCoV-229E, HCoV-OC43, and SARS-CoV-2 ancestral strain and its variants. In terms of characteristics, MMF acted in the early stages of viral infection and inhibited viral replication by blocking purine nucleotide synthesis through interaction with inosine-5'-monophosphate dehydrogenase (IMPDH). Therefore, the antiviral effect of MMF can be reversed by exogenous guanosine. Additionally, MMF in combination with molnupiravir, GC376 or E64d showed synergistic antiviral effects.

Conclusion: MMF and MPA exerted broad-spectrum anti-coronavirus effects by inhibiting IMPDH activity. MMF had a synergistic antiviral effect when combined with other drugs, showing its potential clinical antiviral applications.

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来源期刊
Virology Journal
Virology Journal 医学-病毒学
CiteScore
7.40
自引率
2.10%
发文量
186
审稿时长
1 months
期刊介绍: Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.
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